Labbe A.,Luniversite Laval Hopital Hotel Dieu Of Quebec |
Garand C.,Luniversite Laval Hopital Hotel Dieu Of Quebec |
Cogger V.C.,University of Sydney |
Paquet E.R.,Luniversite Laval Hopital Hotel Dieu Of Quebec |
And 3 more authors.
Journals of Gerontology - Series A Biological Sciences and Medical Sciences | Year: 2011
Werner syndrome is a premature aging disorder caused by mutations in a RecQ-like DNA helicase. Mice lacking the helicase domain of the WRN homologue exhibit many features of Werner syndrome, including a pro-oxidant status and a shorter mean life span. Here, we show that resveratrol supplementation improved the hyperglycemia and the insulin resistance phenotype in these Wrn mutant mice. In addition, resveratrol reversed liver steatosis, lipid peroxidaton, and the defenestration phenotypes observed in such mice. Resveratrol, however, did not improve the hypertriglyceridemia, inflammatory stress, nor extend the mean life span of these mutant mice. Microarray and biologic pathway enrichment analyses on liver tissues revealed that resveratrol mainly decreased lipidogenesis and increased genes involved in the insulin signaling pathway and the glutathione metabolism in Wrn mutant mice. Finally, resveratrol-treated mutant mice exhibited an increase in the frequency of lymphoma and of several solid tumors. These results indicate that resveratrol supplementation might exert at least metabolic benefits for Werner syndrome patients. © The Author 2010. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved.